The goal of this program to produce an enhanced E/P delivered gene adjuvanted DNA vaccine (E-DNA) and combine this with a highly novel polyvalent A, B, C, A/E recombinant protein boost (PPB) as a vaccine platform. The EP focus of this application is to utilize novel surface delivery. By this combination we hypothesize that we will generate an improved spectrum of T and B anti HIV immune responses compared to current HIV vaccine modalities. This project builds on a major innovations and accomplishments by the members of this team that have led to this proposal. The team has worked together productively for multiple years. Furthermore they have an outstanding track record of productivity working with the HVTN. The inclusion of CHAVI investigators as part of the preclinical development immune analysis is a major strength of the program. There are 3 highly interrelated, translational focused, exceptionally novel projects which build on a strong track record of accomplishment together that comprise this program. They are supported by a highly respected and critical protein core as well as seasoned administrative core.